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Print version ISSN 0034-7094
Rev. Bras. Anestesiol. vol.57 no.4 Campinas July/Aug. 2007
Intra- and postoperative tremors: prevention and pharmacological treatment*
Temblores intra y postoperatorio: prevención y tratamiento farmacológico
Viviane Ferreira Albergaria; TSAI; Michelle Nacur Lorentz; TSAII; Frederico Augusto Soares de LimaIII
do Corpo Clínico do Instituto Biocor; Anestesiologista e Co-Responsável
pelo CET do Hospital das Clínicas da UFMG
IIAnestesiologista do Corpo Clínico do Instituto Biocor
IIIME3 da Fundação Hospitalar do Estado de Minas Gerais (FHEMIG)
OBJECTIVES: Tremors can be an adverse effect of the surgical intervention
and anesthesia. The incidence of postoperative tremors varies from 6.3% to 66%.
Young age, male gender, the use of halogenated anesthetics, and prolonged anesthesia
or surgical procedure are related with tremors. Tremors are involuntary and
present as oscillating muscular activity aiming at increasing heat production.
Postoperative tremors are a disagreeable complication related with increased
morbidity. Tremors increase the metabolism, resulting in a 200% to 500% increase
in oxygen consumption.
CONTENTS: The objective of this paper was to discuss the causes, prevention, and treatment of intra- and postoperative tremors in adults and children undergoing general anesthesia or neuroaxis anesthesia for surgical interventions.
CONCLUSIONS: Tremors, along with nausea and vomiting, cause severe discomfort in the recovery room, besides being highly prejudicial because they generate an increase in the metabolism. Although the presence of tremors has not been directly related with cardiac morbidity, its prevention has become the subject of discussion and several scientific reports. Prevention and treatment of tremors should be implemented. Patients with limited cardiovascular reserve could develop lactic acidosis, mixed venous desaturation, and hypoxemia.
Key Words: ANESTHESIA: General, regional; COMPLICATIONS: hypothermia, tremor; TREMOR: prevention, treatment.
Y OBJETIVOS: Los temblores pueden ocurrir como un efecto adverso de la intervención
quirúrgica y anestesia. La incidencia de temblores postoperatorios varía
entre 6,3% y 66%. Pacientes jóvenes, sexo masculino, uso de agentes anestésicos
halogenados y tiempo prolongado de anestesia o procedimiento quirúrgico
están relacionados con temblores. Los temblores son involuntarios y se
presentan como actividad muscular oscilatoria con finalidad de aumentar la producción
de calor. E temblor postoperatorio es una desagradable complicación que
está relacionada con el aumento de la morbidez. El temblor aumenta el
metabolismo resultando en un aumento de 200% a 500% en el consumo de oxígeno.
CONTENIDO: Discute las causas, prevención y tratamiento de los temblores intra y postoperatorio en pacientes adultos y pediátricos sometidos a la intervención quirúrgica bajo anestesia general o del neuroeje.
CONCLUSIONES: Los temblores son, juntamente con náuseas y vómitos, causas de intensa incomodidad en la sala de recuperación pos anestésica, además de potencialmente perjudiciales por generar un aumento de la demanda metabólica. Aunque la presencia de temblores no haya sido directamente relacionada a la morbidez cardiaca, la prevención se ha hecho tema de debate y de varios artículos científicos. La prevención y el tratamiento de temblores deben ser implementados. Pacientes con reserva cardio pulmorar limitada pueden sufrir con la acidosis láctica, falta de saturación venosa mixta e hipoxemia.
In homeothermic species, the thermal regulation system coordinates the defenses against cold and heat, while maintaining internal body temperature within a narrow range, ideal for physiological and metabolic functions. However, the combination of anesthesia and exposure to the cold, can lead to hypothermia and tremors in surgical patients 1,2. Since those tremors are usually self-limiting, do not become chronic, and normally do not have more serious consequences, they are often underestimated.
Postoperative tremors are frequently associated with loss of body heat, although hypothermia by itself does not fully explain them. However, they cause discomfort for the patients and sometimes can lead to complications 3.
Along with nausea and vomiting, tremors are one of the most frequent problems during the initial recovery after general anesthesia 4,5. Tremors are very uncomfortable and psychologically stressing. They can also lead to complications, especially in patients with coronary artery disease, due to an increase in oxygen consumption (O2) by 100% to 600%, increase production of carbon dioxide (CO2), resulting in reduced minute ventilation, increased cardiac output 6, increase in circulating catecholamines (increased heart rate), besides decreasing O2 saturation in mixed venous blood 7-9. There can also be an increase in intracranial and intraocular pressures, interference with the ECG, pulse oximetry 10, blood pressure, increase in metabolism, and cause lactic acidosis 7-9.
Postoperative tremors can be of two types: the first corresponds to the tremor associated with thermal regulation that is associated with vasoconstriction, being a physiological response to central or peripheral hypothermia 11,12 that develops in the intraoperative period; the second corresponds to the tremor associated with vasodilation or tremor not associated with thermal regulation 13. It has been observed that tremors do not affect only hypothermic patients 14,15 and they can also be present in patients whose temperature is normal 2,16.17 and, on the other hand, many hypothermic patients do not develop tremors. Sessler et al. concluded that postoperative tremors are secondary to thermal regulation 12, are caused by hypothermia, and can also affect normothermic patients who are developing fever 15. However, some tremors during labor 18 and general anesthesia 19 are not related with thermal regulation, and worsen due to undertreated pain 8,20.
More than ten years ago, Crossley 21 enumerated some variables that influence the development of tremors: prolonged surgical procedures, male gender, anticholinergic agents (atropine), spontaneous ventilation, altered physical state (high ASA), more frequent in general surgical procedure than orthopedics, and blood transfusion. He also mentioned that advanced age, and the administration of propofol, alfentanil, or morphine were the most important variables in the protection against tremors.
Several studies suggest that surgery-related factors, as pain and stress, contribute to the genesis of tremors 12. The mechanisms involved with the development of tremors are complex and presumably result from adaptive evolution. There is not one pathway responsible for them; on the contrary, several mechanisms are capable to modulate thermal regulation responses 15.
Intraoperative hypothermia, besides causing severe complications, may prolong hospitalization 22, and can also be associated with a reduction in drug metabolism, delayed awakening from anesthesia, negative nitrogen balance, and tremors 23.
The use of hypothermia as a therapeutic strategy for neuroprotection is still controversial 24. Hypothermia reduces intracranial pressure, increases cerebral perfusion pressure and decreases its metabolism. However, even moderate hypothermia has undesirable side effects, such as tremors and peripheral vasoconstriction, resulting in hemodynamic instability, increase in oxygen consumption, and cerebral and myocardial ischemia.
In humans, moderate hypothermia results in better neurological recovery in patients who survive cardiorespiratory arrest 25,26. The International Liaison Committee on Resuscitation (ILCOR) recommends its use in those cases 27.
Postoperative tremors affect 5% to 65% of patients recovering from general anesthesia 7, and 30% of those undergoing epidural anesthesia 28. They can be tremors associated with thermal regulation or due to the release of cytokines caused by the surgical procedure. Core temperature usually falls from 0.5°C to 1.5°C in the first hour after anesthetic induction. The hypothermia that develops in the first hour after induction of general 29 or neuroaxial 30 anesthesia results primarily from the redistribution of heat from the center to the periphery. Every anesthetic, opioid, and sedative, reduces vasoconstriction and the autonomic control of thermal regulation (tremor threshold), facilitating the development of hypothermia.
In a study of 2,595 adult patients, Crossley 21 detected tremors in 164 (6.5%) and identified male gender and pre-anesthetic medication with anticholinergics as risk factors. The type of anesthetic induction was not considered a risk factor in this study. Another study by Eberhat et al. 31 evaluated 1,340 consecutive patients who underwent surgery under general anesthesia, and observed tremors in 11.9% of them. Risk factors related with postoperative tremors were hypothermia, age, orthopedic surgeries, and prolonged surgical procedures; but age seemed the most important factor. The objective of that study was to develop an algorithm to anticipate tremors; patients undergoing surgical procedures were evaluated, excluding those who presented preoperative hypothermia or those who used drugs that could interfere with thermal regulation (clonidine, meperidine, phenothiazine). The incidence of moderate or severe tremor (grades 3 and 4) was 11.6%. The total incidence of any tremor (including grade 2) was 14.4%. Thermal regulation activity (including vasoconstriction and piloerection) was observed in 17.6%. Among these patients, only 33% complained of being cold. The work used multivariable analysis and found three independent factors that predict the development of tremors: youth, surgeries with endoprosthesis, and low core body temperature. Age was by far the most important risk factor, being responsible for more than 70% of the predictive power of the model. This was not surprising, because thermal regulation response is decreased in the elderly 15.
It is difficult to determine independent risk factors for tremors before surgery, since several variables influence postoperative thermal regulation in the case of volatile 32 or intravenous anesthetics, and sedatives 33. Besides, almost every drug used regularly by patients (antihypertensives, those used in the treatment of diabetes, and coumarin derivatives) seems to offer significant protection against tremors. In fact, the incidence of tremors is decreased in patients taking propranolol 34.
Core temperature contributes 30% to the control of tremors and vasoconstriction, while mean skin temperature contributes 20% 35. Therefore, it is reasonable to assume that, in the absence of a surgical procedure, hypothermia contributes for the development of tremors and that normothermia protects against it 12. The study demonstrated that core temperature had only a slight influence on the development of tremors when compared with age (most important factor), and was compatible with the results of other studies that demonstrated that temperature has a weak predictive power for the development of tremors 36,37. According to the analysis of multifactorial logistic regression, core temperature was not directly related with postoperative tremors in children, while the relative change of perioperative temperature was one of three independent predictors 38. However, tremors in patients whose body temperature is lower than 36°C lasted longer than in those who were warmed up 39.
The study confirmed a previous work 21 that showed that orthopedic surgeries (especially endoprosthesis) using bone cement was an independent risk factor for the development of tremors. A possible explanation would be the release of cytokines (tumor necrosis factor-alpha and interleukin-6) stimulated by the bone cement polymethylmethacrylate 40.
Prolonged surgeries were associated with a higher incidence of tremors. A possible explanation is that these procedures are more complex and invasive. Damaged tissue might release pyrogenic substances that change the trigger point of the thermal regulation system in the postoperative period, leading to the development of tremors 41.
Active intraoperative warming to maintain normothermia is important in the prevention of tremors 42,43. The center of thermal regulation is in the posterior hypothalamus, and its activity is modulated by temperature receptors in the skin, visceras, and in several levels of the neuroaxis 42,44. Every volatile anesthetic produces tremors by changing the tremor threshold 45,46.
During anesthesia, the patient has no thermal regulation responses, because the reflex is inhibited. During recovery, the inhibition disappears and tremors appear when the temperature is below the thermal regulation threshold 47.
TREMORS AND ANESTHESIA
Since hypothermia is one of the predictive factors for the development of tremors, and being an independent risk factor for cardiac morbidity 48, it should be avoided, recognized, and treated. Although it might be beneficial during the intraoperative period, by decreasing metabolism and protecting vital organs from ischemia, when the patient awakes from anesthesia, adrenergic and metabolic responses of thermal regulation are activated, causing postoperative discomfort, tremors, increased bleeding, and increased incidence of infection and cardiovascular effects 49. During the intraoperative period, the incidence of myocardial ischemia and ventricular tachycardia are similar in hypothermic and normothermic patients. On the other hand, during the postoperative period, the incidence of ventricular tachycardia and electrocardiographic changes is greater in hypothermic patients 48. The disparity between the intra- and postoperative periods suggests that anesthesia might have a protective effect against the adverse responses to the stress caused by the cold. There are two response mechanisms of thermal regulation to hypothermia that might be harmful to the cardiovascular system: the adrenergic response with vasoconstriction associated with elevation in blood pressure, and increased metabolic demand related to tremors 50,51. Hemodynamic responses to the vasoconstriction secondary to thermal regulation seem to be similar without anesthesia and with different concentrations of desflurane and isoflurane 52.
CLASSIFICATTION OF TREMORS
The degree of tremors was evaluated and classified according to a qualitative scale in the work of Crossley and Mahajan 36: 0 = without tremor; 1 = without visible muscular activity but with piloerection, peripheral vasoconstriction, or both; 2 = muscular activity affecting only one muscle group; 3 = moderate muscular activity involving more than one muscle group, but without generalized tremors; and 4 = severe muscular activity involving the entire body.
PHARMACOLOGICAL PREVENTION OF TREMORS
Proper warming of the body is not always feasible. Therefore, tremors should be prevented pharmacologically in selected patients.
Several drugs have been studied for the prophylaxis and treatment of tremors, including clonidine, meperidine, ketanserin (an anti-hypertensive drug, and antagonist with high affinity for 5-HT and a1-adrenergic receptors); doxapram (respiratory stimulant); and tramadol and other opioids 15,53. The cholinergic system is probably among the mediators of tremors. Physostigmine, an anticholinesterase drug that crosses the blood-brain barrier, is widely used to treat the central cholinergic syndrome 54. Studies suggest that physostigmine increases the cholinergic neurotransmission by stimulating the hypothalamus-hypophysis-adrenal axis and the medulla of the adrenal gland, inhibiting generalized thermal regulation.
Moderate hypothermia may have undesirable effects, such as tremors and vasoconstriction, and measures to prevent them in the postoperative period might be necessary. There are reports demonstrating that clonidine reduces the incidence of postoperative tremors, but the mechanism of action has not been elucidated 54. The a2-agonists exert their action on a2- adrenergic and imidazolic receptors. The first ones can be found in the brain, spinal cord, and the periphery. In the brain, they are related with sedation; in the spinal cord, with analgesia. The effects of clonidine on post-synaptic a2-receptors in the central nervous system reduces the sympathetic tonus that leads to peripheral vasodilation and hypotension 24. The effects of meperidine on thermal regulation seem to involve a2-adrenergic receptors 41.
Several drugs (meperidine, ketanserin, sufentanil, alfentanil, tramadol, physostigmine, urapidil, nefopam, doxapram, and nalbuphine) have already been tested to prevent or treat tremors 7-9,28,55,56. Meperidine proved to be one of the most effective 56,57, probably by acting on the thermal regulation center 55 or through opioid receptors 15. It is possible that NMDA receptors also modulate thermal regulation in several levels 15. Ketamine, a NMDA antagonist, showed to be capable to inhibit tremors 58.
Treatments established to prevent tremors include several drugs, such as nefopam, a benzoxazocin, that inhibits the reuptake of noradrenaline, dopamine, and serotonin. These drugs are not specific for tremors and exert their action through different mechanisms, such as decreasing the activation of the sympathetic nervous system 9,53,59, adrenal suppression 38, stimulation of opioid receptors, or influencing the serotoninergic system 5,9,15,60.
The cholinergic system is an important pathway that can potentially influence tremors. The hypothalamus and the striated body are the regions in the brain in which physostigmine is more active 61,62. Physostigmine is a central acting cholinesterase inhibitor that interacts with cholinergic muscarinic, serotoninergic, and endorphinergic brain receptors, as well as with µ-opioid agonists and a2-agonists 15. Therefore, it seems to work by increasing central neurotransmission. It seems to be safe and highly effective, with very little side effects that include hemodynamic changes; however, they were not observed in the study, probably due to the slow administration (15 minutes) 62,63.
Besides, physostigmine produced analgesia by releasing b-endorphins 64; and postoperative pain can lead to tremors 20. The dose of physostigmine is usually 2 mg 62,63. Physostigmine reduced significantly the incidence and severity of tremors, as much as nefopam. Cholinergic pathways seem to be involved in the thermal regulation, decreasing tremors without influencing awakening from anesthesia, alertness, and postoperative recovery.
In another study, divided in two stages, Stapelfeldt et al. 24 investigated the use of clonidine in 48 patients undergoing elective neurosurgery. First, they determined, in 14 patients, the dose of clonidine necessary to prevent postoperative tremors after inducing moderate hypothermia (35°C). This dose was 3 µg.kg-1. In the second stage, they investigated whether clonidine, due to its sedative action, would delay awakening from anesthesia in neurosurgeries and, therefore, delay the neurological evaluation. Thirty-four patients who underwent neurological surgeries were randomly distributed in two groups to receive clonidine (3 µg.kg-1) or normal saline when the dura mater began to be sutured. Inhalational anesthetics and the infusion of opioids were discontinued at that moment and propofol was administered to every patient. Recovery of patients was evaluated two hours after the end of anesthesia at the following moments: upon opening his/her eyes, when extubated, regarding obeying commands and orientation in time and space. There were no significant differences between both groups in the duration of post-anesthetic recovery. Systolic blood pressure was lower in the clonidine group, which was statistically significant; however, it was not clinically significant 24. The ideal dose of clonidine has not been determined yet, but small doses may be enough to prevent tremors after moderate hypothermia.
Piper et al. 9 compared clonidine and nefopam in the prevention of tremors and found out that they are equally effective. However, clonidine caused more sedation and delayed awakening, suggesting that nefopam is a better prophylactic drug.
In another systematic revision, Kranke et al. 65 described the efficacy and risks of using drugs to prevent the development of tremors. They analyzed 27 articles (1,348 adults received medication and 931 were controls). The incidence of tremors in the control group was extremely frequent (52%). Clonidine, 65 to 300 µg (1,078 patients), 12.5 to 35 mg of meperidine (250 patients), 35 to 220 mg of tramadol (250 patients), and 6.5 to 11 mg of nefopam (204 patients) were tested in at least three studies each. All of them were more effective when compared with the controls. The studies suggest that less than four patients have to receive prophylactic clonidine in order that one patient does not present tremors after the surgery. For meperidine, nefopam, and tramadol, the efficacy seemed even more convincing. The high prevalence of tremors in patients who were not treated suggests that study populations have a high risk, and might not be representative of the general population. Besides, the high prevalence in this population tends to overestimate the usefulness of therapeutic interventions. Clonidine was tested in more studies than the other drugs, which allowed the evaluation of its dose and the time of administration. To be more effective, it should be administered during induction (and not before) in doses greater than 140 µg 65.
There were limiting factors. First, the mechanism of action against tremors of the drugs analyzed is not completely characterized. Some of them might change the tremor threshold. This has been demonstrated for meperidine 66 and clonidine 67. Second, it was not possible to establish predictive factors for postoperative tremors. Third, like a similar previous study 41, it was necessary to use indirect comparisons to estimate the relative efficacy of the anti-tremor interventions, since there is no gold standard that can be used as a comparison. Fourth, most of the studies had a small cohort, and only 5 of them had 50 patient or more 68,71, and studies with small samples tend to overestimate the efficacy of the treatment. Fifth, the quality of the method used in most of the studies was not satisfactory. And sixth, the report on side effects was poor, but it does not necessarily mean that they were not present. Dal et al. 72 compared low doses of ketamine, meperidine, and placebo in the prophylaxis of tremors. Ninety patients, ages 18 to 65 years, physical status ASA I or II, who underwent general anesthesia for 60 to 180 minutes, were divided in 3 groups of 30 each. Group S received normal saline; Group K received ketamine (0.5 mg.kg-1); and Group P received meperidine (20 mg) 20 minutes before surgery. The tympanic temperature of every patient was greater than 36°C and, therefore, did not require warming. The incidence of tremors was significantly lower in Groups K and P than in Group S, and there were no differences between Groups K and P. The length of time until the first request of analgesics in Group S was much smaller (12 min) than in Groups K (25 min) and P (32 min). Two hours after the end of the procedure, every patient needed analgesics. There were no differences in pain scores among the groups, using the Visual Analogic Scale (VAS), 30 minutes after the end of the surgery. Two patients in Group K had grade 2 tremors and were treated with meperidine, which was effective, probably because its mechanism of action is different, or because the dose of 0.5 mg.kg-1 of ketamine was not enough. Patients did not present adverse effects related to ketamine. This drug might be an alternative for the prophylaxis of postoperative tremors in patients who cannot receive meperidine. Future studies might demonstrate the ideal dose of ketamine for the prophylaxis of postoperative tremors. There were no differences between Groups K and P regarding the prevention of tremors. There was no relationship between axillary temperature and the development of tremors 58.
Ketamin is a NMDA antagonist that is effective in the prevention of tremors, probably through the thermogenesis without tremors pathway, by acting on the hypothalamus, or by a b-adrenergic effect, besides having some effect on the k receptor. A study suggested that the action of meperidine against tremors might be through k receptors, because high doses of naloxone inhibits its action (high doses inhibit mu and kappa receptors), while small doses of naloxone do not (inhibit only mu receptors) 56. The disadvantage of meperidine is the risk of respiratory depression, nausea, and vomiting.
Rohm et al. 73 investigated the effects of physostigmine in the prophylaxis of postoperative tremors, and compared it with nefopam, a drug known to be effective 5. Eighty-nine patients undergoing abdominal or urological surgeries were evaluated. Patients received 2 mg of physostigmine (n = 31), 10 mg of nefopam (n = 30), or normal saline (n = 28). Hemodynamic parameters and temperature were measured at induction and 5, 15, 30, and 60 minutes after arrival in the recovery room. The incidence of tremors was significantly lower after the administration of physostigmine and nefopam (9.7% and 3.3%) than with placebo (53.6%). Time of extubation, hemodynamic parameters, and tympanic temperature were similar in all groups. Only nefopam reduced significantly the incidence of postoperative nausea and vomiting. Physostigmine reduced successfully and safely the incidence and severity of tremors. This success was similar to that of nefopam and it did not delay the recovery of patients.
Another study was undertaken by Hong and Lee 74 with patients undergoing cesarean sections with epidural anesthesia with 8 mg to 10 mg of 0.5% hyperbaric bupivacaine associated with morphine (0.1 mg or 0.2 mg), meperidine (10 mg), or just local anesthetic (LA). The incidence of tremors was greater in patients who received just LA (23.3.%). Those who received meperidine had not only the lowest incidence (3.3%), but tremors were also less severe when compared with those who received morphine (0.1 mg 17%; 0.2 mg 13.3%). The epidural administration of opioids can also be capable of abolishing tremors, although their mechanism of action, influencing tremor threshold, has not been established 75. A study by Abreu et al. 75 compared the incidence of intra- and postoperative tremors in epidural blocks with and without fentanyl. They concluded that adding 100 µg of fentanyl to the LA for the epidural block does not abolish the tremor, but reduces the incidence and severity, without increasing the incidence of nausea and vomiting.
NON-PHARMACOLOGICAL PREVENTION OF TREMORS
Tremors can be treated by warming up the patient, applying radiant heat, or drugs 55.
Among the measures used in the maintenance of body temperature, the warm air blanket can be beneficial and cost effective 43.
Simply covering the patient with a blanket was indicated as a tremor-reducing factor that did not change core temperature 43. Skin temperature is not a predictive factor for tremors. However, it is unquestionable that increasing skin temperature enough can, alone, stop tremors.
TREATMENT OF POSTOPERATIVE TREMORS
The development of tremors is a frequent complication in the recovery room, and several drugs are used to treat it, although their mechanism of action have not been elucidated 41; in a meta-analysis by Kranke et al., meperidine was deemed the most effective drug for the treatment of tremors, and a dose of 25 mg reduced the recurrence of tremors nine times as often as placebo, maintaining an anti-tremor effect for at least 45 minutes. Meperidine was associated with a small increase in side effects, such as nausea, vomiting, and reduction in respiratory rate. In situations that meperidine cannot be used, the authors suggest the use of clonidine (150 µg), ketanserin (10 mg), alfentanil (0.25 mg), or doxapram (100 mg). It should be mentioned that the intraoperative maintenance of body temperature and the use of warm air blankets decreased the need of drugs for the treatment of tremors 76.
In a study with 220 patients aiming at identifying the effective dose of meperidine for the treatment of tremors, Crossley 76 concluded that 0.35 mg.kg-1 is the smallest dose necessary to treat adequately postoperative tremors.
Tramadol has also been used in the past few years to treat tremors and, according to some studies, its efficacy is similar to that of meperidine 77.
Nefopam is a central-acting analgesic benzoxacin that reduces tremors without affecting ventilation, with minimal sedation, and proven efficacy. Contrary to other drugs, it does not cause vasoconstriction, working only in the tremor pathway 78.
TREMORS IN PEDIATRIC PATIENTS
Most of the studies on postoperative tremors are done in adults and, when they are done with children, they include a small number of patients 16. A classical work by Akin et al. 16 with 1,507 children ages 0 to 16 years, undergoing general anesthesia, was undertaken to determine the prevalence of tremors, as well as the triggers and clinical implications. After the surgery, the child was transferred to the recovery room and received oxygen by face mask. The tympanic temperature was measured, the type and duration of the surgery were recorded, as well as the method of anesthetic induction (inhalational, with sevoflurane, or intravenous, with thiopental), age, and association with caudal epidural. The temperature of the operating room and recovery room was maintained between 22°C and 23°C. Of 1,507 children, only 53 (3.5%) developed tremors. There was a statistically significant difference between children with and without tremors regarding length of surgery, body temperature, and age. The type of surgery and gender had no relationship with the prevalence of tremors. The risk of tremors increased with ages above 6 years, use of intravenous agents for induction, and surgeries lasting more than 40 minutes. In 37 out of the 53 patients, tremors improved by rewarming alone; 16 of them needed intravenous meperidine (0.35 mg.kg-1). In this study, the prevalence of tremors in children who received thiopental for induction was significantly greater. However, since these children were older, that could have been a contributing factor. The incidence of tremors was statistically lower in children who received caudal epidural anesthesia.
PREVENTION AND TREATMENT OF TREMORS IN CHILDREN
Kranke et al. 3 proposed an algorithm for the pharmacological prevention and treatment of tremors in children based on studies done in adults, and recommended that hypothermia should be avoided. When a child developed tremor, he/she was treated by rewarming and, if there was no response, they suggested the administration of clonidine (1.5 µg.kg-1) or meperidine (0.35 µg.kg-1) that is, since the treatment of tremors is simple, effective, and low cost, and since prophylaxis is recommended only in high risk patients, it should not be routinely done in children. In their study, Akin et al. 16 did not consider that prophylaxis of tremors in children was necessary, due to the low incidence (3.5%), and it should be treated when present.
Prophylaxis of postoperative tremors is simple and effective. The problem is to evaluate when they should be prevented or treated. Treatment of tremors is also effective; however, many patients presented recurrence of the problem. Since the maintenance of a normal body temperature influences profoundly postoperative tremors, the use of prophylactic drugs is questioned. It seems they should be done only in special cases, such as patients in whom greater oxygen consumption would increase the risk of complications 65.
In a study comparing several drugs isolatedly to prevent tremors, clonidine, meperidine, tramadol, and nefopam were more effective than placebo and, although the incidence of bradycardia, hypotension, and sedation are greater with clonidine, these effects were not observed in the doses used in this study.
The incidence of tremors can be predicted with moderate discriminative power using four risk factors derived from a logistic regression analysis: age (variable with the greatest predictive power), core temperature upon admission to the recovery room, prolonged surgical procedure, and orthopedic procedures.
The pharmacological prophylaxis of postoperative tremors is possible and will only be effective when the risk is too high. This raises the question whether tremors should be prevented or treated. Treatment with meperidine or clonidine is very effective. The option for prophylaxis means the unnecessary administration of drugs to several patients, exposing them to side effects. Since intraoperative body warming and maintenance of core temperature greatly influence the incidence of postoperative tremors 10, the use of pharmacological prophylaxis is questioned. Patients in whom the cardiac supply of oxygen is compromised are a special case; in these cases, pharmacological prophylaxis is preferable, and clonidine should be the rational choice because, besides the anti-tremor effect, it has a favorable effect on the heart 79.
01. Frank SM, Beattie C, Christopherson R et al. Epidural versus general anesthesia, ambient operation room temperature, and patient age as predictors of inadvertent hypothermia. Anesthesiology, 1992;77:252-257. [ Links ]
02. Kurz A, Sessler DI, Narzt E et al. Postoperative hemodynamic and thermoregulatory consequences of intraoperative core hypothermia. J Clin Anesth, 1995;7:359-366. [ Links ]
03. Kranke P, Eberhart LH, Roewer N et al. Postoperative shivering in children: a review on pharmacologic prevention and treatment. Paediatr Drugs, 2003;5:373-383. [ Links ]
04. Buggy D, Higgins P, Moran C et al. Clonidine at induction reduces shivering after general anaesthesia. Can J Anaesth, 1997;44:263-267. [ Links ]
05. Piper SN, Röhm KD, Suttner SW et al. A comparison of nefopam and clonidine for the prevention of postanaesthetic shivering: a comparative, double-blind and placebo-controlled dose-ranging study. Anaesthesia, 2004;59:559-564. [ Links ]
06. Ciofolo MJ, Clergue F, Devilliers C et al. Changes in ventilation, oxygen uptake, and carbon dioxide output during recovery from isoflurane anesthesia. Anesthesiology, 1989;70:737-741. [ Links ]
07. Singh P, Dimitriou V, Mahajan RP et al. Double-blind comparison between doxapram and pethidine in the treatment of postanaesthetic shivering. Br J Anaesth, 1993;71:685-688. [ Links ]
08. Mathews S, Al Mulla A, Varghese PK et al. Postanaesthetic shivering a new look at tramadol. Anaesthesia, 2002;57:394-398. [ Links ]
09. Piper SN, Suttner SW, Schimdt CC et al. Nefopam and clonidine in the prevention of postanaesthetic shivering. Anaesthesia, 1999;54:695-699. [ Links ]
10. Buggy DJ, Crossley AW Thermoregulation, mild perioperative hypothermia and postanaesthetic shivering. Br J Anaesth, 2000; 84:615-628. [ Links ]
11. Lienhart A, Fiez N, Deriaz H Frisson postoperatoire: analyse des principaux facteurs associes. Ann Fr Anesth Reanim, 1992; 11:488-495. [ Links ]
12. Sessler DI, Rubinstein EH, Moayeri A Physiologic responses to mild perianesthetic hypothermia in humans. Anesthesiology, 1991;75:594-610. [ Links ]
13. Horn EP Postoperative shivering; aetiology and treatment. Curr Opin Anaesthesiol, 1999;12:449-453. [ Links ]
14. Camus Y, Delva E, Just B et al. Leg warming minimizes core hypothermia during abdominal surgery. Anesth Analg, 1993; 77:995-999. [ Links ]
15. De Witte J, Sessler DI Perioperative shivering: physiology and pharmacology. Anesthesiology, 2002;96:467-484. [ Links ]
16. Akin A, Esmaoglu A, Boyaci A Postoperative shivering in children and causative factors. Paediatr Anaesth, 2005; 15:1089-1093. [ Links ]
17. Crossley AW Peri-operative shivering. Anaesthesia, 1992; 47:193-195. [ Links ]
18. Panzer O, Ghazanfari N, Sessler DI et al. Shivering and shivering-like tremor during labor with and without epidural analgesia. Anesthesiology, 1999;90:1609-1616. [ Links ]
19. Horn EP, Sessler DI, Standl T et al. Non-thermoregulatory shivering in patients recovering from isoflurane or desflurane anesthesia. Anesthesiology, 1998;89:878-886. [ Links ]
20. Horn EP, Schroeder F, Wilhelm S et al. Postoperative pain facilitates nonthermoregulatory tremor. Anesthesiology, 1999; 91:979-984. [ Links ]
21. Crossley AW Six months of shivering in a district general hospital. Anaesthesia, 1992;47:845-848. [ Links ]
22. Alfonsi A, Nourredine KE, Adam F et al. Effect of postoperative skin-surface warming on oxygen consumption and the shivering threshold. Anaesthesia, 2003;58:1228-1234. [ Links ]
23. Sessler DI Mild perioperative hypothermia. New England J Med,1997;336:1730-1737. [ Links ]
24. Stapelfeldt C, Lobo EP, Brown R et al. Intraoperative clonidine administration to neurosurgical patients. Anesth Analg, 2005; 2005:226-232. [ Links ]
25. Bernard SA, Gray TW, Buist MD et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypotermia. N Engl J Med, 2002;346:557-563. [ Links ]
26. Hypothermia after Cardiac Arrest Study Group Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med, 2002;346:549-556. [ Links ]
27. Nolan JP, Morley PT Vanden Hock TL et al. Therapeutic hypothermia after cardiac arrest: an advisor statement by the Advanced Life Support Task Force of the International Liaison Committee on Resuscitation. Circulation, 2003;108:118-121. [ Links ]
28. Horn EP, Werner C, Sessler DI et al. Late intraoperative clonidine administration prevents postanesthetic shivering after total intravenous or volatile anesthesia. Anesth Analg 1997; 84:613-617. [ Links ]
29. Matsukawa T, Sessler DI, Sessler AM et al. Heat flow and distribution during induction of general anesthesia. Anesthesiology, 1995;82:662-673. [ Links ]
30. Matsukawa T, Sessler DI, Christensen R et al. Heat flow and distribution during epidural anesthesia. Anesthesiology, 1995; 83:961-967. [ Links ]
31. Eberhart LH, Doderlein F, Eisenhardt G et al. Independent risk factors for postoperative shivering. Anest Analg, 2005;101:1849-1857. [ Links ]
32. Xiong J, Kurz A, Sessler DI et al. Isoflurane produces marked and nonlinear decreases in the vasoconstriction and shivering thresholds. Anesthesiology, 1996;85:240-245. [ Links ]
33. Matsukawa T, Kurz A, Sessler DI et al. Propofol linearly reduces the vasoconstriction and shiverig thresholds. Anesthesiology, 1995;82:1169-1180. [ Links ]
34. Lee DS, Shaffer MJ Low incidence of shivering with chronic propranolol therapy. Lancet, 1986;1:500. [ Links ]
35. Cheng C, Matsukawa T, Sessler DI et al. Increasing mean skin temperature linearly reduces the core-temperature thresholds for vasoconstriction and shivering in humans. Anesthesiology, 1995;82:1160-1168. [ Links ]
36. Crossley AW, Mahajan RP The intensity of postoperative shivering is unrelated to axillary temperature. Anaesthesia, 1994;49:205-207. [ Links ]
37. Holdcroft A, Hall GM Heat loss during anaesthesia. Br J Anaesth, 1978;50:157-164. [ Links ]
38. Lyons B, Taylor A, Power C et al. Postanaesthetic shivering in children. Anaesthesia, 1996;51:442-445. [ Links ]
39. Vaughan MS, Vaughan RW, Cork RC Postoperative hypothermia in adults: relationship of age, anesthesia, and shivering to rewarming. Anesth Analg, 1981;60:746-751. [ Links ]
40. Miyaguchi M, Kobayashi A, Iwaki H et al. Human monocyte response to retrieved polymethylmethacrylate particles. J Biomed Mater Res, 2002;62:331-7. [ Links ]
41. Kranke P, Eberhart LH, Roewer N et al. Pharmacological treatment of postoperative shivering: a quantitative systematic review of randomized controlled trials. Anesth Analg, 2002; 94:453-460. [ Links ]
42. Crossley AW Postoperative shivering: the influence of body temperature. BMJ, 1995;311:764-765. [ Links ]
43. Buggy D, Hughes N Pre-emptive use of the space blanket reduces shivering after general anaesthesia. Brit J Anaesth, 1994;72:393-396. [ Links ]
44. Gordon CJ, Heath JE Integration and central processing in temperature regulation. Ann Rev Phsiol, 1986;48:595-612. [ Links ]
45. Sessler DI, Esrael D, Pozos RS et al. Spontaneous postanesthetic tremor does not resemble thermoregulatory shivering. Anesthesiology, 1988;68:843-850. [ Links ]
46. Annadata R, Sessler DI, Tayefeh F et al. Desflurane slightly increases the sweating threshold, but produces marked and non-linear decreases in the vasoconstriction and shivering thresholds. Anesthesiology, 1995;83:1205-1211. [ Links ]
47. Cheong KF, Low TC Propofol and postanesthetic shivering. Anaesthesia, 1995;50:550-552. [ Links ]
48. Frank SM, Fleisher LA, Breslow MJ at al Perioperative maintenance of normothermia reduces the incidence of morbid cardiac events: a randomized clinical trial. JAMA, 1997; 277:1127-1137. [ Links ]
49. Pestel GJ, Kurz A Hypothermia: it's more than a toy. Curr Opin Anesthesiol, 2005;18:151-156. [ Links ]
50. Lopez M, Selsser DI, Walter K et al. Rate and gender dependence of the sweating, vasoconstriction, and shivering thresholds in humans. Anesthesiology, 1994;80:780-788. [ Links ]
51. Macintyre PE, Pavlin EG, Dwersteg JF Effect of meperidine on oxygen consumption, carbon dioxide production, and respiratory gas exchange in postanesthesia shivering. Anesth Analg, 1987;66:751-755. [ Links ]
52. Greif R, Laciny S, Rajek A et al. Blood pressure response to thermoregulatory vasoconstriction during isoflurane and desflurane anesthesia. Acta Anaesthesiol Scand, 2003;47:847-852. [ Links ]
53. Piper SN, Maleck WH, Boldt J et al. A comparison of urapidil, clonidine, meperidine and placebo in preventing postanesthetic shivering. Anesth Analg, 2000;90:954-957. [ Links ]
54. Milam SB, Bennett CR Physostigmine reversal of drug-induced paradoxical excitement. Int J Oral Maxillofac Surg, 1987; 16:190-193. [ Links ]
55. Vanderstappen I, Vandermeersch E, Vanacker B et al. The effect of prophylactic clonidine on postoperative shivering: a large prospective double-blind study. Anaesthesia, 1996; 51:351-355. [ Links ]
56. Wrench IJ, Cavill G, Ward JE et al. Comparison between alfentanil, pethidine and placebo in the treatment of post-anaesthetic shivering. Br J Anaesth, 1997;79:541-542. [ Links ]
57. Terasako K, Yamamoto M Comparison between pentazocine, pethidine and placebo in the treatment of post-anaesthetic shivering. Acta Anaesthesiol Scand, 2000;44:311-312. [ Links ]
58. Sharma DR, Thakur JR Ketamine and shivering. Anaesthesia, 1990:45:252-253. [ Links ]
59. Delaunay L, Bonnet F, Liu N et al. Clonidine comparably decreases the thermoregulatory thresholds for vasoconstriction and shivering in humans. Anesthesiology, 1993;79:470-474. [ Links ]
60. Powell RM, Buggy DJ Ondansetron given before induction of anesthesia reduces shivering after general anesthesia. Anesth Analg, 2000;90:1423-1427. [ Links ]
61. Pappata S, Tavitian B, Traykov L et al. In vivo imaging of human cerebral acetylcholinesterase. J Neurochem, 1996;67:876-879. [ Links ]
62. Horn EP, Standl T, Sessler DI et al. Physostigmine prevents postanesthetic shivering as does meperidine or clonidine. Anesthesiology, 1998;88:108-113. [ Links ]
63. Latasch L, Müller B, Freye E Routinemassige gabe von Physostigmin hat fur die postoperative phase keine bedeutung-eine randomisierte untersuchung zur vigilans zum kreislaufverhalten, muskelzitten und schmerzmittelbedarf. Anasthesiol Intensivmed Notfallmed Schmerzth, 2003;38:528-537. [ Links ]
64. Risch SC, Janowsky DS, Mott MA et al. Central and peripheral cholinesterase inhibition: effects on anterior pituitary and syjmpathomimetic function. Psychoneuroendocrinology, 1986; 11:221-230. [ Links ]
65. Kranke P, Eberhart LH, Roewer N et al. Single-dose parenteral pharmacological interventions for the prevention of postoperative shivering: a quantitative systematic review of randomized controlled trials. Anesth Analg, 2004;99:718-727. [ Links ]
66. Kurz A, Ikeda T, Sessler DI et al. Meperidine decreases the shivering threshold twice as much as the vasoconstriction threshold. Anesthesiology, 1997;86:1046-1054. [ Links ]
67. Nicolaou G, Chen AA, Johnston CE et al. Clonidine decreases vasoconstriction and shivering thresholds, without affecting the sweating threshold. Can J Anaesth, 1997;44:636-642. [ Links ]
68. Eberhart LH, Novatchkov N, Schricker T et al. Clonidin in vergleich zu midazolam zur intravenosen pramedikation von ambulatenten eingriffen. Eine kontrollierte doppelblindstudie bei ASA 1-patienten. Anasthesiol Intensivmed Notfallmed Schmerzther, 2000;35:388-393. [ Links ]
69. Sia S I.V. clonidine prevents post-extradural shivering. Br J Anaesth, 1998;81:145-146. [ Links ]
70. Vanderstappen I, Vandermeersch E, Vanacker B et al. The effect of prophylactic clonidine on postoperative shivering: a large prospective double-blind study. Anaesthesia, 1996; 51:351-355. [ Links ]
71. Weinbroum AA, Geller E Flumazenil improves cognitive and neuromotor emergence and attenuates shivering after halothane, enflurane and isoflurane-based anesthesia. Can J Anaesth, 2001;48:963-972. [ Links ]
72. Dal D, Kose A, Honca M et al. Efficacy of prophylactic ketamine in preventing postoperative shivering. Br J Anaesth, 2005; 95:189-192. [ Links ]
73. Rohm KD, Riechmann J, Boldt J et al. Physostigmine for the prevention of postanaesthetic shivering following general anaesthesia a placebo-controlled comparasion with nefopan. Anaesth, 2005;60:433-438. [ Links ]
74. Hong JY, Lee IH Comparison of the effects of intrathecal morphine and pethidine on shivering after caesarean delivery under combined spinal epidural. Anaesthesia, 2005;60:1168-1172. [ Links ]
75. Abreu MP, Vieira JL, Lutti MN, et al. Incidência de tremor em anestesia com ou sem fentanil: estudo comparativo. Rev Bras Anestesiol, 2004;54:153-161. [ Links ]
76. Wrench IJ, Singh P, Dennis AR et al. The minimum effective doses of pethidine and doxapram in the treatment of post-anaesthestic shivering. Anaesthesia, 1997;52:32-36. [ Links ]
77. Tsai YC, Chu KS A comparation of tramadol, amitriptyline, and meperidine for postepidural anesthetic shivering in parturients. Anesth Analg, 2001;93:1288-1292. [ Links ]
78. Alfonsi P, Adam F, Passard A et al. Nefopam a nonsedative benzoxazocine analgesic, selectively reduces the shivering threshold in unanesthetized subjects. Anesthesiology, 2004; 100:37-43. [ Links ]
79. Stevens RD, Burri H, Tramèr MR Pharmacologic myocardial protection in patients undergoing noncardiac surgery: a quantitative systematic review. Anesth Analg, 2003;97:623-633. [ Links ]
Viviane Ferreira Albergaria
Praça Clemente de Faria, 80 Prado
30410-490 Belo Horizonte, MG
Submitted em 19
de maio de 2006
Accepted para publicação em 23 de março de 2007
* Received from Instituto Biocor, Nova Lima, MG